The effects of topiroxostat on vascular function in patients with hyperuricemia

J Clin Hypertens (Greenwich). 2019 Nov;21(11):1713-1720. doi: 10.1111/jch.13707. Epub 2019 Sep 26.

Abstract

Xanthine oxidoreductase (XOR) inhibitors, such as allopurinol and febuxostat, inhibit the catalysis of serum uric acid (SUA) synthesis. In doing so, they are thought to improve vascular endothelial function in patients with hyperuricemia and cardiovascular risk by reducing increases in SUA and reactive oxygen species levels. We performed a retrospective cohort study to evaluate the effects of topiroxostat, a novel XOR inhibitor, on vascular function measured by flow-mediated dilation (FMD) on ultrasonography. In total, 23 patients with hyperuricemia were enrolled. After approximately 8 weeks, topiroxostat was associated with a significant increase in the peak percentage change in diameter (∆FMD) from 4.53% ± 2.09% to 5.54% ± 3.08% (P = .045). It also significantly reduced the SUA levels from 7.31 ± 1.43 to 5.44 ± 1.11 mg/dL (P < .001). Although further studies are needed to validate these results, it appears that topiroxostat improves vascular endothelial function in patients with hyperuricemia.

Keywords: flow-mediated dilation; hyperuricemia; topiroxostat; vascular function; xanthine oxidoreductase.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biological Availability
  • Blood Flow Velocity / drug effects
  • Enzyme Inhibitors / administration & dosage
  • Enzyme Inhibitors / pharmacokinetics
  • Female
  • Humans
  • Hyperuricemia* / blood
  • Hyperuricemia* / drug therapy
  • Hyperuricemia* / physiopathology
  • Male
  • Middle Aged
  • Nitriles* / administration & dosage
  • Nitriles* / pharmacokinetics
  • Pyridines* / administration & dosage
  • Pyridines* / pharmacokinetics
  • Reproducibility of Results
  • Retrospective Studies
  • Ultrasonography, Doppler / methods
  • Uric Acid / blood*
  • Vasodilation / drug effects*
  • Xanthine Dehydrogenase / antagonists & inhibitors*

Substances

  • Enzyme Inhibitors
  • Nitriles
  • Pyridines
  • FYX-051
  • Uric Acid
  • Xanthine Dehydrogenase